Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5TLTYU)

• DOT Name: Solute carrier family 28 member 3 (SLC28A3)
• Synonyms: Concentrative Na(+)-nucleoside cotransporter 3; CNT 3; hCNT3
• Gene Name: SLC28A3
• UniProt ID: S28A3_HUMAN
• PDB ID: 6KSW
• Pfam ID: PF07670 ; PF07662 ; PF01773
• Sequence:
  MELRSTAAPRAEGYSNVGFQNEENFLENENTSGNNSIRSRAVQSREHTNTKQDEEQVTVE
  QDSPRNREHMEDDDEEMQQKGCLERRYDTVCGFCRKHKTTLRHIIWGILLAGYLVMVISA
  CVLNFHRALPLFVITVAAIFFVVWDHLMAKYEHRIDEMLSPGRRLLNSHWFWLKWVIWSS
  LVLAVIFWLAFDTAKLGQQQLVSFGGLIMYIVLLFLFSKYPTRVYWRPVLWGIGLQFLLG
  LLILRTDPGFIAFDWLGRQVQTFLEYTDAGASFVFGEKYKDHFFAFKVLPIVVFFSTVMS
  MLYYLGLMQWIIRKVGWIMLVTTGSSPIESVVASGNIFVGQTESPLLVRPYLPYITKSEL
  HAIMTAGFSTIAGSVLGAYISFGVPSSHLLTASVMSAPASLAAAKLFWPETEKPKITLKN
  AMKMESGDSGNLLEAATQGASSSISLVANIAVNLIAFLALLSFMNSALSWFGNMFDYPQL
  SFELICSYIFMPFSFMMGVEWQDSFMVARLIGYKTFFNEFVAYEHLSKWIHLRKEGGPKF
  VNGVQQYISIRSEIIATYALCGFANIGSLGIVIGGLTSMAPSRKRDIASGAVRALIAGTV
  ACFMTACIAGILSSTPVDINCHHVLENAFNSTFPGNTTKVIACCQSLLSSTVAKGPGEVI
  PGGNHSLYSLKGCCTLLNPSTFNCNGISNTF
• Function: Sodium-dependent, pyrimidine- and purine-selective. Involved in the homeostasis of endogenous nucleosides. Exhibits the transport characteristics of the nucleoside transport system cib or N3 subtype (N3/cib) (with marked transport of both thymidine and inosine). Employs a 2:1 sodium/nucleoside ratio. Transports uridine. Also able to transport gemcitabine, 3'-azido-3'-deoxythymidine (AZT), ribavirin and 3-deazauridine.
• Tissue Specificity: Expressed in pancreas, bone marrow, trachea, mammary gland, liver, prostate, and regions of intestine, brain, lung, placenta, testis, kidney, and heart.
• Reactome Pathway:
  Azathioprine ADME (R-HSA-9748787)
  Ribavirin ADME (R-HSA-9755088)
  Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane (R-HSA-83936)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Solute carrier family 28 member 3 (SLC28A3) increases the Cardiotoxicity ADR of Doxorubicin.	[10]
Daunorubicin	DMQUSBT	Approved	Solute carrier family 28 member 3 (SLC28A3) increases the Cardiotoxicity ADR of Daunorubicin.	[10]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
3-iodothyronamine	DM3L0F8	Investigative	Solute carrier family 28 member 3 (SLC28A3) affects the uptake of 3-iodothyronamine.	[11]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Solute carrier family 28 member 3 (SLC28A3).	[1]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Solute carrier family 28 member 3 (SLC28A3).	[2]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Solute carrier family 28 member 3 (SLC28A3).	[3]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Solute carrier family 28 member 3 (SLC28A3).	[4]
ANW-32821	DMMJOZD	Phase 2	ANW-32821 increases the expression of Solute carrier family 28 member 3 (SLC28A3).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Solute carrier family 28 member 3 (SLC28A3).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Solute carrier family 28 member 3 (SLC28A3).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Solute carrier family 28 member 3 (SLC28A3).	[8]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Solute carrier family 28 member 3 (SLC28A3).	[9]

References

• [1] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [2] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [3] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [4] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [5] Human Mincle Binds to Cholesterol Crystals and Triggers Innate Immune Responses. J Biol Chem. 2015 Oct 16;290(42):25322-32. doi: 10.1074/jbc.M115.645234. Epub 2015 Aug 20.
• [6] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [7] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [10] Recommendations for genetic testing to reduce the incidence of anthracycline-induced cardiotoxicity. Br J Clin Pharmacol. 2016 Sep;82(3):683-95. doi: 10.1111/bcp.13008. Epub 2016 Jun 30.
• [11] Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.